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Nat Commun ：肥胖相关|发现Foxp1蛋白调控棕色及亮色脂肪细胞分化与产热的重要作用

2019-11-09 兮 BioArt

Foxp1蛋白调控棕色亮色脂肪细胞分化产热重要作用
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在全球范围内，肥胖及肥胖相关代谢性疾病如二型糖尿病患者，等正以惊人的速度不断增长，严重影响了人们的生活质量。棕色 (brown adipocyte) 及亮色 (beige adipocyte) 脂肪细胞是进行适应性产热的重要场所，其主要功能是消耗能量。通过激活棕色及亮色脂肪其产热功能，对于对抗肥胖及二型糖尿病具有重要意义。肾上腺素信号通路 (Adrenergic signaling) 是中枢神经系

在全球范围内，肥胖及肥胖相关代谢性疾病如二型糖尿病患者，等正以惊人的速度不断增长，严重影响了人们的生活质量。棕色 (brown adipocyte) 及亮色 (beige adipocyte) 脂肪细胞是进行适应性产热的重要场所，其主要功能是消耗能量。通过激活棕色及亮色脂肪其产热功能，对于对抗肥胖及二型糖尿病具有重要意义。肾上腺素信号通路 (Adrenergic signaling) 是中枢神经系统调控脂肪适应性产热的重要信号通路。肾上腺素信号通路通过诱导棕色脂肪PGC1α/UCP1的表达和活化，促进棕色脂肪产热；同时也可以促进白色脂肪进行脂裂解。肾上腺素受体，包括α/β受体，是该信号通路的重要组成部分。

脱敏作用是细胞的一种自我保护机制，可使细胞免受过量信号所带来的伤害。脱敏作用通常通过受体的磷酸化，受体的内化及下调受体的mRNA水平来降低受体的密度。其中，肾上腺素β受体Adrb1及Adrb2通过内吞来实现其脱敏作用，而β3型受体Adrb3由于缺少PKA及GPCR 激酶作用的磷酸化位点，所以不能进行内吞作用，而之前的研究显示Adrb3确实存在脱敏现象，但具体机制还不是很清楚。

2019年11月7日，上海交通大学Bio-X研究院郭熙志组与瑞金医院的王计秋课题组合作在Nature Communications在线发表了题为Foxp1 controls brown/beige adipocyte differentiation and thermogenesis through regulating β3-AR desensitization 的研究论文，该工作阐明了Foxp1在调控棕色及亮色脂肪细胞分化及适应性产热方面发挥的重要作用，并揭示了Foxp1通过调控β3-AR的转录，从而调控其脱敏过程的机制。

研究人员发现，在脂肪细胞中特异性敲除 Foxp1 提高了棕色脂肪细胞分化及活性，加快了白色脂肪细胞棕色化进程，敲除小鼠整体能量代谢增强并可以抵抗高脂饮食所诱导的肥胖及胰岛素抵抗；相反，在脂肪细胞中特异性过表达 Foxp1，破坏了小鼠的适应性产热能力而导致其在高脂饮食作用下更易肥胖。

深入研究发现，棕色及亮色脂肪细胞中Adrb3/cAMP/Erk1/2 信号通路的激活可以促进Foxp1的表达；Foxp1作为转录因子通常在细胞核中发挥作用，它通过与在脂肪细胞分化及产热中发挥核心作用的Prdm16-C/EBPβ 复合物相互作用，并结合在靶基因的启动子部位，共同抑制了Adrb3及PPARγ 的转录，在转录水平上参与Adrb3的脱敏作用调节，在脂肪细胞发育及适应性产热方面发挥重要作用，为研究治疗肥胖及慢性代谢性疾病提供了新的理论线索。

原始出处：
Pei Liu, Sixia Huang, Shifeng Ling, et al.Foxp1 controls brown/beige adipocyte differentiation and thermogenesis through regulating β3-AR desensitization.Nature Communications .Published: 07 November 2019.volume10, Article number: 5070 (2019)

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    2020-02-02 yilong5287542

    #脂肪细胞分化#

    0

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    2020-05-05 liye789132251

    #Nat#

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    2020-02-13 liuli5079

    #COMMUN#

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    2020-03-30 jiyangfei

    #重要作用#

    0

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    2019-11-11 hb2008ye

    #脂肪细胞#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1810274, encodeId=2fc818102e4ea, content=<a href='/topic/show?id=16838438192' target=_blank style='color:#2F92EE;'>#脂肪细胞分化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84381, encryptionId=16838438192, topicName=脂肪细胞分化)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=87f580, createdName=yilong5287542, createdTime=Sun Feb 02 12:29:00 CST 2020, time=2020-02-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1883984, encodeId=be71188398429, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Tue May 05 19:29:00 CST 2020, time=2020-05-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2087623, encodeId=d942208e62399, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Thu Feb 13 07:29:00 CST 2020, time=2020-02-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2023542, encodeId=208e2023542d1, content=<a href='/topic/show?id=57ce9605ef6' target=_blank style='color:#2F92EE;'>#重要作用#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96057, encryptionId=57ce9605ef6, topicName=重要作用)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8e4c53, createdName=jiyangfei, createdTime=Mon Mar 30 06:29:00 CST 2020, time=2020-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1400930, encodeId=5e791400930ee, content=<a href='/topic/show?id=8fde8438079' target=_blank style='color:#2F92EE;'>#脂肪细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84380, encryptionId=8fde8438079, topicName=脂肪细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=hb2008ye, createdTime=Mon Nov 11 04:29:00 CST 2019, time=2019-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1570282, encodeId=c8b815e028217, content=<a href='/topic/show?id=a66ae7809b1' target=_blank style='color:#2F92EE;'>#细胞分化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77809, encryptionId=a66ae7809b1, topicName=细胞分化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=653c15636865, createdName=karmond, createdTime=Mon Nov 11 04:29:00 CST 2019, time=2019-11-11, status=1, ipAttribution=)]
    2019-11-11 karmond

    #细胞分化#

    0